Gastrinomas are the most common symptomatic, malignant PET in patients with or without MEN1 and sufficient numbers of these patients have been entered into our protocols to allow systematic assessment. Studies are now underway, evaluating the natural history of these tumors including the presentation and initial diagnosis and definition of factors determining prognosis. Our studies have identified a cohort of 25% of patients in whom the gastrinomas have aggressive growth and 25% who have multiple endocrine neoplasia type 1 (MEN1). Two prospective longterm studies of fasting gastrin levels (FSG) and gastrin provocative tests were published which for the first time establish clinical guidelines based on these paramenters for management and diagnosis based on prospective studies. One study involved results of FSG in 309 NIH patients with comparison of 2229 cases from the literature and the second of provocative test results in 293 NIH patients which was compared to 537 in the literature. These results were correlated for the first time with clinical findings, other lab studies and tumoral features and identified important clinical guidelines that will improve diagnosis and management of these patients. A new criterion for positivity of secretin provocative testing was proposed which for the first time was based on a detailed analysis of specificity and sensitivity which should help in the earlier diagnosis of these patients which is now delayed 6 years. A longterm prospective study of patients with ZES with MEN1 demonstrated these patients are at increased risk of developing severe esophageal disease and the premalignant condition, Barrett's esophagus. Detailed analysis of clinical variables provided evidence this increased risk was due to delayed diagnosis and inadequate treatment of the acid hypersecretion. The surgical treatment of patients with gastrinomas is controversial because they frequently are not cured. Our longterm surgical studies demonstrated for the first time this year that routine surgical exploration for cure increases patient survival which was entirely due to resection of the gastrinoma and therefore should be done in all patients.The results of a number of the NIH prospective studies were used in colloboration with the European Neuroendocrine Tumor network to develop both consensus statements, position papers and treaement guidelines.